A lack of non-invasive markers to detect cartilage degradation has prevented a fundamental understanding of the development of osteoarthritis (OA), as well as early diagnosis of and intervention in OA. Unlike convention Magnetic Resonance Imaging (MRI) that measures or compares only cartilage image intensity, area or volume, Microscopic MRI (muMRI) is well-suited for the quantitative study of articular cartilage. The muMRI can produce quantitative images not only of water distribution, but also of unique parameters reflecting molecular level information in the tissue at microscopic resolution. In a recent muMRI study using the spin-spin relaxation time (T2), we demonstrated quantitatively at 14muM pixel resolution that (1) there is a unique T2 anisotropy in canine articular cartilage. Our goal is to use T2 relaxation as a sensitive and non-invasive MRI marker to study the tissue structure and molecular interactions in articular cartilage. We propose a number of specific aims (1) to determine the relationship between the T2 anisotropy by muMRI and the histological orientation of the collagen fibrils; (2) to study the heterogeneity of the T2 anisotropy at different load-bearing areas in a joint; (3) to detect the localized anisotropies of the T2 distribution profile in cartilage; (4) to determine the role of the proteoglycan component of cartilage on the T2 anisotropy; (5) to compare the T2 characteristics of normal cartilage with that of naturally lesioned cartilage; and (6) to determine the zone-specific characteristics in cartilage during loading. In combination, these six aims will yield otherwise unavailable new information to elucidate various biophysical, biochemical and biological mechanisms and properties in this important biomaterial at the molecular level. Our proposal is unique in combining the high-resolution nature of muMRI, the quantitative T2 measurement, and histological information. The perfection of the muMRI techniques is the greatest strength of our work. We can now examine the tissue properties in individual histological zones in cartilage non-invasively and at microscopic resolution, thus contributing to the understanding, and ultimately, prevention of arthritic disease.